53 Nakajo-Nishimura syndrome: the first African case

Abstract Nakajo-Nishimura syndrome is a hereditary autoinflammatory disorder caused by an autosomal recessive homozygous mutation of the PSMB8 gene, which encodes the immunoproteasome subunit beta 5i. The clinical manifestations of NNS are mainly pernio-like skin rashes, nodular erythema, lipodystrophy, clubbed fingers, remittent fever, hepatosplenomegaly, and basal ganglia calcifications. Here we are reporting a case of NNS in an 11-year-old girl, who lives in eastern Algeria, born from a first-degree consanguineous marriage, she presented with erythematous patches on her face and her back, nodular erythema on her neck, swollen and painful fingers with acrocyanosis and recurrent fever that mainly occurred in cold weather. The patient received long-term treatment with low-dose glucocorticoids, along with immunomodulatory drugs (hydroxychloroquine with methotrexate), partial improvement clinically and biologically was observed. Colchicine was added to her treatment, with increased prednisone doses when she recently developed an AA amyloidosis. Our patient was diagnosed clinically with NNS because she exhibited six of the eight characteristics. To the best of our knowledge, this is the first case of NNS in Africa.


Background
Childhood-onset Systemic Lupus Erythematosus (cSLE) is a rare but severe multisystem autoimmune/inflammatory disease that can affect any organ system and cause significant damage, disability and/or death. Corticosteroids are one of the important therapeutic weapons for childhood Systemic Lupus Erythematosus (SLE). Prednisone doses are increased during flare-ups of lupus disease, and then progressively reduced to reach a threshold dose in order to avoid the harmful effects of this treatment in growing children. The oral route is by far the most used over prolonged periods, however corticosteroid boluses are recommended in the treatment of severe acute attacks of the disease. Objective Assess the use of corticosteroids in childhood systemic lupus erythematosus (SLE) and the risk of steroid-related damage.

Methods
Patients with childhood -onset SLE (n ¼ 83) treated at paediatric rheumatology centre were followed for 36 months. Information on medication use, disease activity as measured by SLEDAI was collected.

Results
Eighty-three (83) patients were studied. Female: male ratio was 1:49. Mean ages at lupus onset and diagnosis were respectively: 10, 12 (AE3,88_ and 11, 3 (AE3,62) years. Corticosteroids were used in 92% of cases in oral form and on 37% of cases as a bolus of high dose intravenous methylprednisolone. The indication of corticoids bolus was significantly related to severe forms (p ¼ 0,001), high disease activity (p ¼ 0, 00008), and macrophage activation Syndrome (p ¼ 0, 0006). The doses varied between 0.5-1 g/1.73m2. The mean initial disease activity in these patients was 30 AE 10, while that found after taking the treatment was 12.9 AE 15. The decrease was statistically significant (p ¼ 0, 000001). More than half of our patients were on high dose oral corticosteroids (2 mg/kg/d) and only 1/5 of the patients benefited from a dose of (1 mg/kg/day). The use of corticosteroids has been associated with significant side effects, including growth delay (22%), cushingoid obesity (58%), stretch marks (49%), osteoporosis (33%), femoral head osteonecrosis (1%), infections (54%). The association of certain side effects with a high dose of oral corticosteroids (2 mg/kg/day) was significant in this case cushingoid obesity (p ¼ 0, 0003), stretch marks (p ¼ 0.014).

Conclusion
Corticosteroids are the mainstay of therapy for prompt control of acute disease related inflammation in patients with SLE; they remain the firstline treatment for significant lupus manifestations, especially severe forms and life-threatening situations Higher dosage and longer duration of therapy, which are common in SLE, result in greater risk of adverse effects. Their use wisely is the guarantee of a better response and the reduction of deleterious effect.

Introduction
The increasing use of biologics in chronic inflammatory diseases is accompanied by an increased risk of infectious complications. Our objective was to determine the predictive factors for the occurrence of infection in patients on biotherapy.

Methods
We conducted a single-center retrospective study in an internal medicine department over a period of 14-year [2009-2022], including the records of patients treated with a biologic agent presenting at least one infectious episode.

Results
During the study period, 20 patients among 50 treated with biologic agent had at least one infection episode. The patient mean age was 50.8 AE 12.1  years and the male to female ratio was 1:2. The mean age at biotherapy first use was 43 AE 12.1 [17-68] years. Infections occurred after a mean duration of 12 months [0.5-36] after the initiation of biotherapy. Eleven patients were followed for chronic inflammatory bowel disease, three patients for ankylosing spondylitis, three patients for vasculitis, two patients for rheumatoid arthritis and one patient for systemic scleroderma. Only three patients were diabetic and two had chronic pulmonary disease. Thirteen patients (65%) were treated by TNFa inhibitors and 35% with anti CD20 (Rituximab). Among TNFa inhibitors, seven infections occurred in patient treated with infliximab (41%), six with adalimumab (35%) and four with etanercept (24%). At the time of infection, half of the patients were treated by corticosteroid with a median dose of 32 mg/d [5-60] and a median duration of 11 months , while 40% of the patients were on conventional immunosuppressive therapy. The infection was severe, requiring hospitalization in eight cases (40%). A statistically significant correlation was found between the occurrence of infection and a duration of anti-TNFa treatment <6 months (p ¼ 0.003) and history of crohn's disease (p ¼ 004). Age >50 years at the time of biotherapy introduction did not correlate with a higher risk of infection (p ¼ 0.7) Conclusion Screening for infections in patient treated with biologic agents must be systematic, especially at the treatment initiation, in order to ensure better compliance and efficacy of the biotherapy.

Introduction
The prognosis of chronic inflammatory diseases has been transformed by the use of biologic drugs. However, there is evidence of an increased risk of infection in patients undergoing biotherapy. The objective of our study was to investigate the frequency and the severity of infections in patients on biotherapy.

Results
We identified 50 patients treated with biologic therapy among 76 patients. The patient's mean age was 48 yearsAE 12.5 [23-76] and male to female ratio (M: F) was 1 :6. The mean age at initiation of biotherapy was 41.3 AE 11.6 [17-68] years. The molecules used were TNFa inhibitors in 82% of cases, rituximab in 14% of cases and tocilizumab in 4%. Infectious complications were identified in 20 patients. Infections occurred after a mean duration of 12 months [0.5-36] after the initiation of biotherapy. They affected the skin in nine cases, the bronchopulmonary tract in seven cases, the central nervous system in four cases, the gastrointestinal tract in three cases, and the upper respiratory tract in two cases. The infection was bacterial in 16 cases (64%), viral in five cases (20%) and fungal in four cases (16%). We report five cases of tuberculosis (TB), including four cases of pulmonary TB and one case of neuro-meningeal TB. The infection was severe, requiring hospitalization in only eight cases (32%). The median duration of hospitalization was 12 days . The infectious episode led to temporary interruption of biotherapy in six cases and definitive interruption in two cases. No deaths were noted.

Conclusion
Our study confirms the increased susceptibility to infections in patients treated with biologics. These infections, often bacterial, are in the majority of cases benign. However, tuberculosis remains frequent.